A few of the latest (99-00) articles on prion. . .

Mechanism

Shows that the conformation of the PrP protein when bound to cellular membranes is significantly different from that of the free protein.

Morillas, M et al. Membrane environment alters the conformational structure of the recombinant human prion protein. Journal of Biological Chemistry. 274(52): 36859-65, 1999 Dec 24.

Proposes mechanism for neuronal death based on the interaction with the distributed cellular prion proteins. Suggests the need for a third protein.

Martins VR. A receptor for infectious and cellular prion protein. Brazilian Journal of Medical and Biological Research. 32(7): 853-9, 1999 Jul.

Shows certain hydrophobic sequences to be influential in the mutant conformation of the prions.

Jobling, MF et al. The hydrophobic core sequence modulates the neurotoxic and secondardy structure properties of the prion peptide 106-126. Journal of Neurochemistry. 73(4): 1557-65, 1999 Oct.

Shows the role of astrocytes in protecting neurons from lutamate toxicity.

Brown, DR. Prion protein peptide neurotoxicity can be mediated by astrocytes. Journal of Neurochemistry. 73(3): 1105-13, 1999 Sep.

Shows that mutant PrP remain near the cell membrane because of glycolipid attachment.

Narwa, R et al. Prion proteins carrying pathogenic mutations are resistant to phospholipase cleavage of their glycolipid anchors. Biochemistry. 38(27): 8770-7, 1999 Jul 6.

Refutes the previous hypothesis that brain injury can lead to neurodegradation.

Doh-ura et al. Brain injury does not modify transmissible spongiform encephalopathy caused by intraperitoneal inoculation with Fukuoka-1 strain. Journal of General Virology. 80 (Pt 6): 1551-6, 1999 Jun.

Emphasizes the need to understand the mechanism of the conformational change and its role in trafficking.

Lehmann, S et al. Trafficking of the cellular isoform of the prion protein. Biomedicine and Pharmacology. 53(1): 39-46, 1999.

Identifies homologous PrP regions among species to explain cross-species trasmission.

Priola, SA. Prion protein and species barriers in the transmissible spongiform encephalopathies. Biomedicine and Pharmacology. 53(1): 27-33, 1999.

Suggests that an increase in brain DNA vulnerability may play a role in neuron loss. Although PrP plaques were not found to damage DNA.

Ferrer, I. Nuclear DNA fragmentation in Creutzfeldt-Jakob disease: does a mere positive in situ nuclear end-labeling indicate apaptosis? Acta Neuropathologica. 97(1): 5-12, 1999 Jan.

Studied the potential role of apoptosis as the reason for a lack of immune response against the prions in CJD. Located regions of cell apoptosis and found a correlation with neuronal loss.

Gray, F et al. Neruonal apaptosis in Creutzfeldt-Jakob disease. Journal of Neuropahology and Experimental Neurology. 58(4):321-8, 1999 Apr.

Suggests that the specific type of prion is what determines the neuropathology of CJD.

Puoti, G et al. Sporadic Creutzfeldt-Jakob disease: co-occurrence of different types of PrP(Sc) in the same brain. Neurology. 53(9):2173-6, 1999 Dec 10.

Diagnosis

Emphasized the need for monoclonal antibodies to diagnose prion diseases. Immunized mice with DNA and live attenuated virus to induce the production of monoclonal antibodies.

Krasemann, S et al. Generation of monoclonal antibodies against prion proteins with an unconventional nucleic acid-based immunization strategy. Journal of Biotechnology. 73(2-3): 119-29, 1999 Aug 20.

Emphasizes the need for monoclonal for detection of prion diseases. Shows the C-terminus portion of the prion protein as immunogenetic in all species.

Rubenstein, R et al. Immune surveillance and antigen confromation determines humoral immune response to the prion protein immunogen. Journal of Nurovirology. 5(4): 401-3, 1999 Aug.

Demonstrates constitutive expression of 14-3-3 proteins in hopes that it can serve as a detector for CNS damage, but proves to not be useful in screening for prion diseases.

Satoh, J. et al. The 14-3-3 protein detectable in the cerebrospinal fluid of patients with prion detectable in the cerebrospinal fluid of patients with prion-unrelated neurological diseases is expressed constitutively in nerurons and glial cells in culture. European Neurology. 41(4): 216-25, 1999.

Developed a new and more sensitive technique for screening prion diseases during the incubation period.

Schulz-Schaeffer, WJ. The paraffin-embedded tissue blot detects PrP(Sc) early in the incubation time in prion diseases. American Journal of Pathology. 156(1): 51-6, 2000 Jan.

Treatment

Suggests that the trigger for conformational change in prions maybe similar in Alzheimer's, and both may be similarly treatable.

Soto, C. Alzheimer's and prion disease as disorders of protein confromation: implications for the design of novel therapeutic approaches. Journal of Molecular Medicine. 77(5): 412-8, 1999 May.

Describes teh role of a polyene antibiotic, amphotericin B, in TSEs. Suggests amphotericin can reduce both the acumulation and incubation period of prion disease in animals.

Mange, A. Effect of amphotericin B on wild-type and mutated prion proteins in cultured cells: putative mechanism of action in transmissible spongiform encephalopathies. Journal of Neurochemistry. 74(2) 754-62, 2000 Feb.

Transmission

Presents evidence that BSE may have been passed from cattle to humans to cause neurodegenerative disease. Shows other evidence of a lack of species barrier with scrapie also.

Scott, MR et al. Compelling transgenetic evidence for transmission of bovine spongifrom encephalopathy prions to humans. Proceeding of the National Academy of Sciences USA. 96(26): 15137-42, 1999 Dec 21.

Explains what measures have been established to prevent BSE from coming to the USA.

Tan, L et al. Risk of transmission of bovine spongiform encephalopathy to humans in the United States: report of the Courncil on Scientific Affairs. American Medical Association. JAMA. 281(24): 2330-9, 1999 Jun 23-30.

Clinical cases

Describes the conditions of the mother and daughter and shows that neither one carried a mutation in the prion protein gene. Uncertain whether these two cases occurred by chance or by genetic risk.

Worrall BB et al. Mothers with amyotrophic lateral sclerosis and daughter with Creutzfeldt-Jakob disease. Archives of Neurology. 56(12): 1502-4, 1999 Dec.

Reported case of the unusual initial presentation of depression in CJD.

Jiang, TT et al. Sporadic Creutzfeldt-Jakob disease presenting as major depression. Southern Medical Journal. 92(8): 807-8, 1999 Aug.

Documented the clinical and pathological presentation of the first Austrian family with FFI.

Almer, G et al. Fatal familial insomnia: a new Austrian family. Brain. 122 (Pt. 1): 5-16, 1999 Jan.

vCJD

The following articles describe the new variant (vCJD) and its connection to BSE:

Schonberger, LB. New variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Infections Disease Clinics of North America. 12(1): 111-112, 1998 Mar.

Keohane, C. The human prion diseases. A review with special emphasis on vew variant CJD and comments on surveillance. Clinical and Experimental Pathology. 47(3-4): 125-32, 1999.

Will, RG et al. Deaths from variant Creutzfeldt-Jakob disease. Lancet 353(9157): 939, 979, 1999 Mar 20.

Collinge, J. Variant Creutzfeldt-Jakob disease. Lancet 354(9175):317-23, 1999 Jul 24.